Sub-inhibitory concentrations of metronidazole alter the proteomic profile and biological effects of extracellular vesicles from Clostridioides difficile.

Zhaoxia Ran, Xiaojie Ruan, Yafei Pan, Liru Wang, Gang Li

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Article in BMC microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

5 authors.

Zhaoxia RanCenter of Medical Laboratory, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.

Xiaojie RuanNingxia Institute of Clinical Medicine, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia, 750004, China.

Yafei PanCenter of Medical Laboratory, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.

Liru WangCenter of Medical Laboratory, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China. yuejnx@163.com.

Gang LiCenter of Medical Laboratory, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China. ligang@nyfy.com.cn.

Funding

Key Research and Development Program of Ningxia 2023BEGO2003

6 · The paper itself

Abstract

backgroundColonization with C. difficile is common in patients with inflammatory bowel disease (IBD). The use of antibiotics can trigger the transition from colonization to active infection, complicating IBD management and presenting challenges for the diagnosis of C. difficile infection (CDI). This study aims to investigate the effects of metronidazole-exposed outer membrane vesicles (EVs) derived from a toxigenic C. difficile strain with no detectable production of toxins A (TcdA) and B (TcdB) under the tested conditions on both the parental strain and host cells.

methodsEVs were isolated from C. difficile (ATCC 43255) by ultracentrifugation. EVs from untreated bacteria were compared with those from bacteria exposed to subinhibitory concentrations of metronidazole (1/4 and 1/8 MIC); the latter were designated as metronidazole-induced EVs (Mi-EVs). EVs were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and ELISA. Data-independent acquisition (DIA) proteomics was used to identify differentially produced proteins among the EV

resultsMetronidazole exposure significantly promoted EVs secretion. Notably, only EV

conclusionsSub‑inhibitory concentrations of metronidazole promote the secretion of C. difficile EVs, which in turn enhance bacterial biofilm formation, host cell viability, and inflammatory responses in a concentration‑dependent manner, while also inhibiting cell migration in a concentration‑dependent manner. These findings offer insights into the complex interplay between antibiotics, colonizing C. difficile strains, and the host in the context of IBD.

Indexed as

Clostridioides difficileExtracellular VesiclesMetronidazoleAnti-Bacterial AgentsBacterial ProteinsBiofilmsCaco-2 CellsCell SurvivalHumansParticle SizeProteomicsAnti-Bacterial AgentsBacterial ProteinsMetronidazoleBioactivitiesClostridium difficileExtracellular vesiclesMetronidazoleSub-inhibitory concentrations

Identifiers

PMID42121031

DOI10.1186/s12866-026-05123-3

PMCPMC13339388

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.